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Fig 1.

The contrasting pattern of geographic jumps, hotspots and global distribution of influenza A viral subtypes.

The heatmaps: A) H13 (green), B) H16 (purple) and C) highly pathogenic avian influenza H5 (red), indicate the frequency of transitions between locations estimated using a discrete trait phylogenetic model and the number of location transitions was determined using Markov jumps. The proportion of time the virus spends in each location (center panel) is indicated by the bar charts with each subtype showing a uniquely different geographic distribution. The global distribution of each subtype is depicted by shading on the maps (right panel). Lines indicate the route of inter-hemispheric virus flow and represent the branching pattern of internal and external nodes of the underlying phylogenetic tree. Basemap made with Natural Earth (https://www.naturalearthdata.com).

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Fig 2.

The occurrence of influenza A viral subtypes over a 10-year period in Alaska reflect neutral and non-neutral evolutionary processes.

A) The temporal pattern consists of two H16 clades (blue: Northern Europe, and purple: Atlantic-Mississippi) that alternate, with introductions of H13 from East Asia (green) and South America (yellow). Geographic origins were determined by most recent common ancestor (MRCA) phylodynamic analysis. B) Genetic diversity of H13 through time C) relative to H16. D) Cross-reactivity of anti-influenza antibodies from Cordova gulls and Minto Flats ducks determined by hemagglutination inhibition (HI) assay. Many antibodies against H13 and H16 were cross-reactive, while few sera recognized H5 low pathogenic virus. E) Antigenic properties of H13, H16 and H5 clades mapped onto two-dimensional space. Virus clades positioned centrally (i.e. H13 from South America) were more cross-reactive than viruses located at the edges (i.e. H5 from Pacific-Central, H13 from East Asia). Circle markers (solid) are size-scaled according to the prevalence of each clade in the Cordova gull population, or their absence (outline). F) Conceptual diagram of the antigenic distance between subtypes relative to prevalence. Gulls are proposed as the reservoir host for H13 and H16, which are antigenically related and overlap resulting in cross-reactivity and competition between H13 and H16. G) Conversely, ducks (and geese and swans) are proposed as the reservoir for highly pathogenic avian influenza H5. No antigenic overlap occurs between HPAI H5, H13 and H16, such that gulls are largely immuno-naïve to HPAI H5. Animal silhouettes from http://phylopic.org.

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Fig 3.

Host jumps and spillover of influenza A viral subtypes at the wild-domestic interface reflects co-evolution with the reservoir host.

The heatmaps: A) H13 (green), B) H16 (purple) and C) HPAI H5 (red), indicate the frequency of transitions between host pairs estimated using a discrete trait phylogenetic model and the number of transitions between species/taxa was determined using Markov jumps. Host interfaces between wild and domestic birds (middle panel) are inferred based on host transitions that are well supported by Bayes Factors (BF). Dashed lines indicate known but infrequently sampled transmissions that could not be included in the analysis due to low sample size. Transition rates between host pairs are shown in the box and whisker plots (only the most strongly supported rates are shown). Large variation in transition rates is observed for HPAI H5N1 with highest rates between wild birds, followed by domestic poultry. In contrast, transition rates for H13 and H16 are lower with consistent patterns observed between host pairs for each subtype. Animal silhouettes from http://phylopic.org.

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Fig 4.

Ecologically divergent hosts contribute to the diffusion and geographic expansion of influenza A virus.

A) The diffusion rates of highly pathogenic avian influenza (HPAI) H5 (red), B) H13 (green) and C) H16 (purple). D) Comparison of two dispersal metrics of HPAI H5: viral diffusion (km/year) and viral wavefront distance (km) plotted for each host type (round markers). The red line indicates the negative relationship between viral diffusion and wavefront distance of HPAI H5 based on regression analysis, with grey shading indicating the 95% confidence interval. E) Viral wavefront distances for HPAI H5 fluctuate over time with a large peak during 2005–2006 and a gradual increase from 2010 onwards. Dispersal rates (km/year) and wavefront distance (km) were estimated using a joint continuous geographic and discrete host diffusion model. Wild bird outbreak data are courtesy of the World Organisation for Animal Health. Available from: https://wahis.oie.int/#/home.

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